In previous disclosures, I described methods for achieving the goal of delivering gas-supersaturated liquids into a variety of environments in a manner which stabilizes the dissolved gas, so that cavitation nucleation does not occur at the exit port of the delivery system.
In the medical environment, regional tissue hypoxia, despite normal respiratory function, is a pathologic substrate responsible for many serious conditions. Hyperbaric oxygen therapy may provide clinical benefit in the treatment of regional ischemia associated with a wide variety of medical problems, but it is limited to 90 minutes/day at 2.5 bar because of the potential for pulmonary oxygen toxicity. Intravenously injected perfluorochemical emulsions may increase the oxygen content of plasma, but do not increase the partial pressure of oxygen in arterial blood. Attempts to infuse dilute solutions of hydrogen peroxide into blood result in uncontrolled foaming during its decomposition by tissue catalase.
In the setting of arterial occlusion, restoration of blood flow may not be possible or may result in tissue hemorrhage and edema, which increases the distance for oxygen diffusion. For other clinical settings, such as radiation-resistant hypoxic neoplasms, radiation-injured tissue adjacent to neoplasms, and a variety of non-healing wounds or infections, arterial occlusion is not a consideration. At present, no interventional technique is available for treatment of regional tissue hypoxia when local blood flow cannot be normalized.
Myocardial ischemia occurs transiently in the majority of patients subjected to coronary angioplasty procedures, including both balloon angioplasty and newer modalities such as directional atherectomy, rotational atherectomy, and stent placement. The duration of balloon inflation is usually determined by the severity of myocardial ischemia, rather than by the operator's estimate of the potential utility of longer balloon inflations. Typically, evidence of severe ischemia, commonly chest pain and ECG changes and occasionally hemodynamic or electrical instability, requires that the operator deflate the balloon in approximately 60 to 120 seconds. For anatomically difficult lesions, such as type B and C lesions, which presently comprise approximately 1/2 of all lesions treated with angioplasty, longer periods of balloon inflation are frequently desirable for the first balloon inflation.
In addition, following the initial brief inflation in many lesions, including morphologically uncomplicated ones, a longer balloon inflation is frequently desirable because of a suboptimal luminal result. Although luminal morphology following stent deployment is usually satisfactory, attempts to advance a stent crimped on a deflated balloon into a tortuous vessel may also be associated with a prolonged period of ischemia.
Autoperfusion balloon catheters permit much longer periods of balloon inflation in most patients in whom this approach is used. However, blood flow through these catheters is inadequate when the systemic arterial pressure is low and may be inadequate in some patients despite a normal blood pressure. The deflated profile of autoperfusion balloon catheters, particularly at the distal balloon end, is relatively bulky compared to standard balloon catheters. As additional drawbacks, it is usually necessary to withdraw the guidewire from the autoperfusion balloon to facilitate perfusion, and the catheters are relatively expensive. Despite these problems, 17% of all coronary balloon catheters used in the U.S. today are autoperfusion catheters. As autoperfusion catheters have been technically refined, such as the development of the monorail system, their utilization has increased.
Occasional instances of myocardial ischemia occur during angioplasty despite achievement of an adequate luminal result. For example, multiple emboli are produced during rotational atherectomy, and depression of myocardial performance may be reduced for many hours as a result. Balloon angioplasty is successful in restoration of an adequate lumen in the vast majority of patients presented with an acute myocardial infarction. But a "no reflow" phenomenon occasionally occurs, very likely as a result of intramyocardial hemorrhage, edema, and perhaps neutrophil entrapment of the microvasculature.
Hemmingsen and co-workers two decades ago demonstrated that water, under static conditions, can be supersaturated with a variety of gases, including oxygen at a partial pressure as great as 140 bar, without bubble formation upon release to 1 bar. Application of high hydrostatic pressure is the most effective means for elimination of cavitation nuclei. Alternative means such as filtration, prolonged standing, boiling, or application of a vacuum are less effective for this purpose. An important mechanism responsible for the high tensile strength of water, in the absence of cavitation nuclei, is the fact that the formation or growth of a bubble at the molecular level (e.g., on the order of 50 .ANG. diameter) requires large pressures, in theory greater than 1 kbar, to overcome the effect of the surface tension of water (Laplace relationship).
The studies of Hemmingsen and prior investigators of the ability to supersaturate water with a gas, without cavitation formation upon release to 1 bar, have been performed under static conditions. Mechanical disturbance of the metastable fluid was noted by previous workers to result in bubble evolution. It was probably assumed that any attempt to eject the fluid into a 1 bar environment would be accompanied by a similar problem. What is now needed is a way to eject gas-supersaturated aqueous solutions from a high pressure vessel into a 1 bar environment without associated bubble formation in the effluent.